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Screening for Birth Defects in the First Trimester


Everything you need to know about first-trimester screening

By Elaine Brown, MD


Historically prenatal screening was offered primarily to women older than 35. These mothers were offered amniocentesis, which at that time was the only available option. Amniocentesis is a test that checks for birth defects and genetic problems in the developing baby. It involves inserting a needle into the amniotic sac (a protective, liquid-filled sac that surrounds the baby in the womb) and removing a small amount of the liquid (amniotic fluid). Although considered safe, the test does pose potential risks, including miscarriage (which can result because of infection in the uterus), the water breaking prematurely or premature labor.

The age of 35 was chosen because, at this age, the risk of a fetal congenital abnormality (which the test helps detect) was equal to the risk of a procedure-related complication due to the amniocentesis. In other words, the risk/benefit ratio tipped at this age to favor testing.

In reality, because the total number of babies born to women younger than 35 years old is so much greater than the number born to older women, most babies with congenital anomalies are born to women younger than 35. Obviously, amniocentesis, though it remains the gold-standard diagnostic test, is not a desirable screening tool for all women. The procedure, which requires insertion of a needle through the maternal abdominal wall directly into the fluid surrounding the fetus, is uncomfortable, invasive and is best delayed until the second trimester. For this reason, clinicians continue to search for reliable alternative methods of screening for Down's syndrome and other fetal genetic abnormalities that can safely be performed earlier in a woman’s pregnancy.

Presently, the most efficient and widely-used screening test is the "quad" screen. Made up of a panel of four blood analytes (alpha-fetoprotein [afp], human chorionic gonadotropin [hCG], unconjugated estriol, and inhibin-a), it is accurate, reliable and non-invasive. The chief disadvantage is that, as with the amniocentesis, the "quad" screen must be delayed until the second trimester. Additionally, results are difficult to interpret in multiple gestations (twins and higher).

Recently, interest has been directed toward first-trimester screening. A combination of ultrasound and serum analytes has been implemented as a tool in some centers. Though the optimal sequence of reporting results to the expectant parents remains controversial, there are definite benefits to having reliable data as early as possible in pregnancy. Early reassurance will reduce the number of pregnancies put at risk by invasive tests, and will permit maximum options for management in affected pregnancies.

The "nuchal translucency" is a normal fluid-filled space at the back of the fetal neck. With proper use of ultrasound technique, this space and its overlying skin can be accurately measured in most pregnancies between 10 and 14 weeks gestational age. Abnormalities in this measurement correlate well with fetal Down's syndrome, other fetal aneuploidies and fetal major cardiac anomalies. Additionally, it is known that pregnancies affected by fetal Down's syndrome are associated with higher levels of free beta-hCG and lower levels of pregnancy-associated plasma protein-a (PAPP-A).

For a given pregnancy with a combination both of a normal ultrasound study and normal values of beta-hCG/PAPP-A, clinicians can feel comfortable recommending deferral of invasive testing. Alternatively, abnormal values alert clinicians to recommend confirmatory testing with chorionic villus sampling (CVS) or amniocentesis.

Major disadvantages of first-trimester screening include expense — the ultrasound component is technically difficult to perform and must be done by specially trained technicians — and the need for an additional blood test in the second trimester to complete the evaluation. The "nuchal translucency" and PAPP-A/beta-hCG combination does not screen for spina bifida or ventral wall defects, therefore most authorities continue to recommend an alpha-fetoprotein the second trimester. While no single option is ideal for every pregnancy, first-trimester screening with "nuchal translucency" and free beta-hCG/PAPP-A, has definite advantages when early results are desirable.


Published on March 6, 2014.


Dr. Elaine Brown completed her residency in obstetrics and gynecology at Harvard. She has more than 15 years of experience in private practice.